Field of the Invention
The present invention relates generally to the use of γ-glutamyl-D-cysteine as a cytoprotective agent to prevent reperfusion injury of the blood-brain barrier that may contribute to hemorrhagic transformation due to thrombolysis following an ischemic stroke. The γ-glutamyl-D-cysteine can be used alone or used in combination with an agent that inhibits the reverse movement of Na/Ca exchange in the blood-brain barrier such as 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulphonate (KB-R7943).
Background of the Invention
In the United States, someone experiences a stroke every minute, and dies from stroke-related complications approximately every three minutes. Strokes may be ischemic or hemorrhagic, but most are due to interrupted blood flow to the brain, resulting in hypoxia. Thus, the treatment for cerebral ischemia accompanying stroke includes therapies to re-establish blood flow. Surprisingly, reperfusion following cerebral ischemia may cause damage to cerebral capillaries (the blood-brain barrier, 63) that can precipitate cerebral edema and ensuing neuropathologies, and may contribute to cerebral bleeding termed hemorrhagic transformation (85, 86). Thus, the cure may actually augment the disease. This appears to be especially true if reperfusion is delayed several hours, and current practice is to avoid reperfusing a patient after approximately 3-4.5 hours of ischemia (1, 88). Recent evidence has verified that using tissue plasminogen activator (t-PA) to dissolve clots is an effective treatment for stroke, if administered within the three hour interval (1). Unfortunately, statistics reveal that 95% of stroke victims are not treated in time. Thus, it is clear that finding a way to prevent the potential side-effects associated with thrombolysis would be a significant and life-saving contribution. We have shown that γ-glutamyl cysteine is an antioxidant that contributes to inhibition of reperfusion injury of cerebral capillaries (U.S. Pat. No. 7,956,037). The present invention discloses the use of γ-glutamyl-D-cysteine to prevent reperfusion injury of the blood brain barrier that may contribute to hemorrhagic transformation due to thrombolytic treatment of ischemic stroke. γ-glutamyl-D-cysteine can be used alone or used in combination with an agent that inhibits the reverse movement of Na/Ca exchange in the blood-brain barrier such as 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulphonate (KB-R7943).
These and other aspects and attributes of the present invention will be discussed with reference to the following drawings and accompanying specification.